Cilostazol combats lipopolysaccharide‐induced hippocampal injury in rats

Role of AKT/GSK3β/CREB curbing neuroinflammation

verfasst von
Doaa Abou El-ezz, Waleed Aldahmash, Tuba Esatbeyoglu, Sherif M. Afifi, Marawan Abd Elbaset, Norsharina Ismail
Abstract

Neuroinflammation is important in the pathophysiology of several degenerative brain disorders. This study looked at the potential neuroprotective benefits of cilostazol, a phosphodiesterase inhibitor, against LPS-induced hippocampus damage in rodents and the principal molecular involvement of AKT/GSK3β/CREB signaling pathways. Behavioral tests revealed that cilostazol successfully corrected LPS-induced neurobehavioral impairments. Furthermore, cilostazol therapy lowered hippocampal levels of amyloid beta 1-42 (Aβ1-42) and p-Tau protein, both of which are critical pathological indicators of neurodegenerative disorders. Furthermore, cilostazol administration suppressed LPS-induced rises in hippocampus caspase-3 and NF-B levels while elevating rat B-cell/lymphoma 2 (BCL2) and brain-derived neurotrophic factor (BDNF) levels, which are implicated in neuronal survival and synaptic plasticity. Cilostazol treatment also restored the decreased phosphorylation of protein kinase B (p-AKT) and reduced the elevated levels of phosphorylated glycogen synthase kinase-3 beta (p-GSK3β) and cAMP response element-binding protein (CREB) in the hippocampus of LPS-Treated rats. Histopathological examination revealed that cilostazol ameliorated LPS-induced brain damage with reduced neuronal loss and gliosis. Immunohistochemistry analysis showed a decrease in Iba-1 expression, indicating a reduction in microglial activation in the cilostazol-Treated group compared to the LPS group. The findings advocate that cilostazol exerts neuroprotective effects against LPS-induced hippocampal injury by modulating the AKT/GSK3β/CREB pathway and curbing neuroinflammation. Cilostazol may hold promise as a therapeutic agent for neuroinflammatory conditions associated with neurodegenerative diseases.

Organisationseinheit(en)
Institut für Lebensmittelwissenschaft und Humanernährung
Externe Organisation(en)
October 6 University
King Saud University
Università di Bologna
National Research Centre (NRC)
Typ
Artikel
Journal
Advances in Pharmacological and Pharmaceutical Sciences
Band
2024
Anzahl der Seiten
10
Publikationsdatum
26.09.2024
Publikationsstatus
Veröffentlicht
Peer-reviewed
Ja
ASJC Scopus Sachgebiete
Pharmakologie (medizinische), Biochemie, Pharmakologie, Toxikologie und Pharmazie (insg.), Organische Chemie
Elektronische Version(en)
https://doi.org/10.1155/2024/3465757 (Zugang: Offen)